Pain is the most common symptom leading patients to consult a physician in the United States. According to the 2012 National Health Interview Survey, over 100 million adults report experiencing pain within the past 3 months, and approximately 50% of these individuals reported that the impact of their pain was moderate or severe. Chronic pain is associated with both direct (e.g., health care) and indirect (e.g., disability) costs that have been estimated to range from $560-635 billion annually. Although considerable progress has been made in understanding the pathophysiologic mechanisms of pain, the most widely prescribed medications for acute and chronic pain?non-steroidal anti-inflammatory drugs and opioid analgesics?have major shortcomings, including modest efficacy and significant risks that can limit long-term use. Consequently, there is a compelling public health need for the development of treatments with improved efficacy and safety. Unfortunately, many analgesic treatments examined in recent randomized clinical trials have failed to show efficacy. The explanations for these results are unknown, raising questions about the ability of clinical trials to distinguish efficacious treatments from placebo or less efficacious treatments (i.e., assay sensitivity). Patient characteristics, clinical trial research methods, outcome measures, approaches to data analysis, and statistical power may all play a role in accounting for difficulties in demonstrating the benefits of efficacious treatments. The identification of specific clinical trial characteristics associated with greater assay sensitivity and the development of outcome measures with greater validity can provide the foundation for an evidence-based approach to the design of clinical trials, not only of pain treatment but also in other therapeutic areas. The primary objective of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations, Opportunities, and Networks (ACTTION) public-private partnership is to facilitate the development of novel analgesic, anesthetic, addiction, and peripheral neuropathy interventions with improved efficacy and safety. ACTTION is a multidisciplinary collaboration that prioritizes research and other initiatives to achieve this objective. The major activities of the ACTTION partnership include conducting systematic reviews, consensus meetings, and methodologically-focused studies as well as developing and qualifying novel clinical outcome assessments with the aim of increasing the assay sensitivity and informativeness of clinical trials. The results of these efforts have the potential to inform and accelerate the development of improved treatments for pain, anesthesia and sedation, addiction, and peripheral neuropathy.